Investigation of some variations of superoxide dismutase gene family in Turkish sporadic amyotrophic lateral sclerosis patients

Abstract Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease caused by the death of motor neurons in the late stage of life and there is currently no effective treatment. To date, there has been much research into the association of ALS and a wide range of genes, including superoxide dismutase (SOD) 1 gene mutations. The SOD family of enzymes (SOD1, 2 and 3) are enzymes which are critical to the most important antioxidant system, protecting cells against reactive oxygen species (ROS). In this study, Asp90Ala and Gly93Ala mutations for SOD1, Ala(-9)Val and Ile58Thr variations for SOD2 and Arg202Leu mutation for SOD3 were investigated in sporadic ALS (SALS) patients and controls. Genotyping of 124 SALS patients and 124 controls was performed with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In SOD1 one patient was homozygous for the previously reported Asp90Ala mutation while no patients, or controls, had the Gly93Ala mutation. Statistical analysis of the data revealed that there was no allelic association between the cases and healthy controls for Ala(-9)Val polymorphism (p=0.538) in SOD2. In addition, no Ile58Thr mutation was found in any subject. Interestingly, two SALS patients were heterozygous for the SOD3 mutation, Arg202Leu. To the best of our knowledge there are no studies into the role of SOD3 mutations in ALS. Thus, this is the first report of an association between SOD3 Arg202Leu mutation and SALS in two patients, suggesting that this mutation may play a role in the pathology of ALS.